Novel ganglion cell marker B3GNT6: A step forward in Hirschsprung's disease diagnosis.

Hirschsprung's (HSCR) disease, also known as aganglionic megacolon, or congenital intestinal aganglionosis affects roughly 1 out of every 5000 newborns. It is a birth defect characterized by the partial or complete loss of ganglion cells in the myenteric and submucosal plexus of the distal intestine which leads to ineffective peristalsis, constipation, and obstruction. Clinical assessment and radiological observations might imply HSCR disease, but definitive diagnosis requires biopsy interpretation and confirmation of ganglion cell loss.

Depolymerization of Waste Polycarbonates to Value-Added Products.

Additive free aminolysis method developed for the depolymerization/upcycling of polycarbonates. We report here chemical recycling of polycarbonate under ambient conditions to get its monomer bisphenol A, monoaminocarbamate and biscarbamates in 1 : 2 : 1 ratio respectively. By employing the secondary amine as the aminating reagent, facilitates the depolymerization to work under additive/catalyst free conditions.

Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer.

Background: Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models.

Emerging Anti-Inflammatory Attributes of Curcumin: A Novel Paradigm and Ameliorative Attributes for the Treatment of Osteoarthritis.

Strong oxidant, curcumin, is diferuloyl methane; a member of the class of phenols known as curcuminoids that give Indian medicinal plants their characteristic turmeric-yellow hue. Over 5000 years ago, curcumin was first employed in the traditional Indian medical system. A growing amount of investigation reveals that curcumin has several pharmacological characteristics, including anticancer, hepatoprotective, anti-inflammatory, antioxidant, and antibacterial properties.

Regional Variation of the CD4 and CD8 T Cell Epitopes Conserved in Circulating Dengue Viruses and Shared with Potential Vaccine Candidates.

As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes are known, less is understood about which of these epitopes are conserved among circulating dengue viruses and also shared by potential vaccine candidates. As India emerges as the epicenter of the dengue disease burden and vaccine trials commence in this region, we have here aligned known dengue specific T cell epitopes, reported from other parts of the world with published polyprotein sequences of 107 dengue virus isolates available from India.

Statistical estimation of noise induced hearing loss among the drivers in one of the most polluted cities of India.

In the present study, an attempt has been made to assess the impact of vehicular noise upon the 3-wheeler tempo drivers and to know whether there is any relationship between hearing loss and cumulative noise exposure. For this purpose, 3-wheeler tempo drivers (Exposed group) and non-commercial light motor vehicle car drivers (Unexposed group) were chosen as study subjects. Three traffic routes were selected to assess the noise level during waiting and running time in the exposed and unexposed groups.

B cell repertoire sequencing of HIV-1 pediatric elite-neutralizers identifies multiple broadly neutralizing antibody clonotypes.

Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants.

Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype.

Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of an infectious 3b cDNA clone.

HCV genotype 3b is a difficult-to-treat subtype, associated with accelerated progression of liver disease and resistance to antivirals. Moreover, its prevalence has significantly increased among persons who inject drugs posing a serious risk of transmission in the general population. Thus, more genetic information and antiviral testing systems are required to develop novel therapeutic options for this genotype 3 subtype.

Targeting of oncogenic AAA-ATPase TRIP13 reduces progression of pancreatic ductal adenocarcinoma.

Thyroid hormone receptor-interacting protein 13 (TRIP13) is involved in cancer progression, but its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. Thus, we assessed the expression, functional role, and mechanism of action of TRIP13 in PDAC. We further examined the efficacy of TRIP13 inhibitor, DCZ0415, alone or in combination with gemcitabine on malignant phenotypes, tumor progression, and immune response.

Barriers of household toilet utilization among toilet owners in a rural area of Northern India: An analytical cross-sectional study.

Background: Open defecation continues to prevail among toilet owners despite effective implementation of the Swachh Bharat Mission (Gramin). We conducted this study to determine toilet utilization rates and learn about the barriers to toilet use in the rural areas. By understanding the barriers, physicians can provide targeted education and become better equipped to manage their patients' conditions and advocate for their demands.

Estimation of Access to Safe Drinking Water to Households in Etawah District: A Cross-Sectional Study.

Context: Unsafe drinking water causes diarrheal disease and environmental enteropathy. The quality of water is determined by its physical, chemical, and biological characteristics. Water sources have a significant impact on household members' health, particularly children.

Oxazoline/amide derivatives against : experimental, biological and computational investigations.

Tuberculosis (TB) is a treatable contagious disease that continuously kills approximately 2 million people yearly. Different oxazoline/amide derivatives were synthesized, and their anti-tuberculosis activity was performed against different strains of Mtb. This study designed the anti-Mtb compounds based on amide and oxazoline, two different structural moieties.

Functional and transcriptional heterogeneity within the massively expanding HLADRCD38 CD8 T cell population in acute febrile dengue patients.

CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR CD38 phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection.

Erratum: Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody.

[This corrects the article DOI: 10.1016/j.isci.

Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody.

The structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations of 15.

Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients.

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients.

Patients And Methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected.

Prediction of human protein interactome of dengue virus non-structural protein 5 (NS5) and its downstream immunological implications.

Unlabelled: The non-structural protein 5 (NS5) is the most conserved protein among flaviviruses, a family that includes the dengue virus. It functions both as an RNA-dependent RNA polymerase and an RNA-methyltransferase and is therefore essential for the replication of viral RNA. The discovery that dengue virus NS5 protein (DENV-NS5) can also localize to the nucleus has resulted in renewed interest in its potential roles at the host-virus interface.

Signaling pathways and molecular process of natural polyphenols in the amelioration of inflammatory bowel disease: A privileged scaffold in new drug discovery.

Background: GIT is seriously affected by inflammatory bowel disease (IBD), which is characterized by extreme inflammation and an imbalance in a person's healthy life span. The frequency of occurrence of such chronic diseases as IBD would continue to increase. In the past decade, increasing attention has been paid to polyphenols from natural sources have been shown to serve as successful therapeutic agents for altering the signalling pathways linked to IBD and oxidative stress.

BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis.

Unlabelled: Because survival of patients with metastatic colorectal cancer remain poor, there is an urgent need to identify potential novel druggable targets that are associated with colorectal cancer progression. One such target, basic leucine zipper and W2 domains 2 (BZW2), is involved in regulation of protein translation, and its overexpression is associated with human malignancy. Thus, we investigated the expression and regulation of BZW2, assessed its role in activation of WNT/β-catenin signaling, identified its downstream molecules, and demonstrated its involvement in metastasis of colorectal cancer.

Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways.

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics.

Vasoactive-ventilation-renal score and outcomes in infants and children after cardiac surgery.

Introduction: There is a need to index important clinical characteristics in pediatric cardiac surgery that can be obtained early in the postoperative period and accurately predict postoperative outcomes.

Methodology: A prospective cohort study was conducted in the pediatric cardiac ICU and ward on all children aged <18 years undergoing cardiac surgery for congenital heart disease from September 2018 to October 2020. The vasoactive-ventilation-renal (VVR) score was analyzed to predict outcomes of cardiac surgeries with a comparison of postoperative variables.